The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive Humans

Abstract

The renin-angiotensin-aldosterone (RAAS) and renal dopaminergic systems interact to maintain sodium balance. High NaCl intake increases renal synthesis of dopamine and dopaminergic receptor activity, decreasing epithelial sodium transport, whereas sodium deficit activates the RAAS, increasing epithelial sodium transport. We tested the hypothesis that attenuation of the natriuretic effect of dopamine D 1 -like receptors during salt restriction results in part from increased RAAS activity in seven salt-resistant normotensive adults using a double-blind placebo-controlled balanced crossover design. All subjects attained sodium balance on low (50 mmol Na + /day) and high (300 mmol Na + /day) NaCl diets, administered 4 weeks apart. Sodium, potassium, lithium, para-aminohippurate, and creatinine clearances were measured before, during, and after a 3-hour infusion of fenoldopam, a D 1 -like receptor agonist, with and without pretreatment with enalapril, an angiotensin converting enzyme inhibitor. On the high NaCl diet, fenoldopam-induced natriuresis was associated with the inhibition of renal proximal and distal tubule sodium transport. On the low NaCl diet, fenoldopam decreased renal distal tubule sodium transport but did not cause natriuresis. The addition of enalapril to fenoldopam restored the natriuretic effect of fenoldopam and its inhibitory effect on proximal tubule sodium transport. Thus, on a high NaCl diet fenoldopam causes natriuresis by inhibiting renal proximal and distal tubule transport, but on a low NaCl diet the increased RAAS activity prevents the D 1 -like receptor from inhibiting renal proximal tubule sodium transport, neutralizing the natriuretic effect of fenoldopam. These results demonstrate an interaction between the renin-angiotensin and renal dopaminergic systems in humans and highlight the influence of dietary NaCl on these interactions. During salt depletion, sodium balance is maintained by increased activity of several systems, including the renin-angiotensin-aldosterone (RAAS) and sympathetic nervous systems.

Sodium balance, circadian BP rhythm, heart rate variability, and intrarenal renin-angiotensin-aldosterone and dopaminergic systems in acute phase of ARB therapy

“…; Natarajan et al. ), since our study population were on a relatively low‐salt diet. The interaction between the intrarenal RAAS and dopaminergic system can be altered by dietary salt intake, and both systems play an important pathophysiological role in development of salt‐sensitive hypertension, and thus, nondipper circadian BP rhythm.…”

G Protein–Coupled Receptor Kinases: Crucial Regulators of Blood Pressure

“…The dopaminergic system and the renin–angiotensin system are important regulators of sodium balance and blood pressure, which are relevant to the pathogenesis and/or maintenance of hypertension . The dopaminergic system exerts a paracrine regulatory role on renal sodium transport in the proximal tubule via its 5 receptor subtypes.…”

“…The dopaminergic system and the renin-angiotensin system are important regulators of sodium balance and blood pressure, which are relevant to the pathogenesis and/or maintenance of hypertension. 13,[15][16][17][18][54][55][56][57]59,[71][72][73][74][75][76][77][78] The dopaminergic system exerts a paracrine regulatory role on renal sodium transport in the proximal tubule via its 5 receptor subtypes. Dopamine receptors, pharmacologically grouped into D 1 -like (D 1 and D 5 ) and D 2 -like (D 2 , D 3 , and D 4 ) receptors, as with the Ang II receptors (AT 1 R and AT 2 R), are expressed in brush border and basolateral membranes of renal proximal tubules.…”

“…In contrast to the stimulatory effect of Ang II on sodium transport in renal proximal tubules, the major consequence of the activation of dopamine receptors is the inhibition of sodium transport. 13,[15][16][17][18][54][55][56][57]59,[71][72][73][74][75][76][77][78] Increasingly, studies show that GRK4 plays an important physiological role in the long-term control of blood pressure and in sodium homoeostasis via the regulation of the renal D 1 R, D 3 R, and AT 1 R.…”

Effects of Fenoldopam in the Pediatric Population: Fluid Status, Serum Biomarkers, and Hemodynamics: A Systematic Review and Meta-Analysis

“…When fenoldopam binds to the receptor, the α subunit dissociates from the intracellular domain of the receptor activating adenylate cyclase that converts ATP (adenosine triphosphate) to cAMP (cyclic adenosine monophosphate). 3 In the cytoplasm, cAMP, the main second messenger in the pathway, activates protein kinase A that phosphorylates and inactivates myosin light-chain kinase (MLCK). The inactivation of MLCK blocks the cross-bridge formation between actin a myosin causing relaxation of the smooth muscle cell.…”